Researchers say they have discovered how the malaria parasite gains a foothold inside the human body, causing the life-threatening illness. The finding could lead to a new treatment for malaria - using a drug that’s already in clinical trials for use against another condition.
After taking a blood meal, experts say the malaria-infected female Anopheles mosquito injects about 1,000 parasites into the bloodstream.
The microorganisms quickly reproduce after each one enters a red blood cell, according Doron Greenbaum, a professor of pharmacology at the University of Pennsylvania.
“Each parasite divides from one into say 24 to 32 parasites in 48 hours. So you can imagine that an initial thousand parasites can grow very fast,” Greenbaum said.
Greenbaum says he and his colleagues discovered that inside the red blood cells, the parasites utilize a series of proteins to reproduce. After sapping the cells of their nutrient machinery, the new-born parasites burst through the cell walls and back into the blood stream, where they infect new blood cells, producing millions more offspring. After a one- to two-week incubation period, the parasitic infection causes the often fatal symptoms associated with malaria, including very high fevers, chills and sweats.
The discovery of this protein pathway inside the red cell could lead to the use of a new oral medication -- called sotrastaurin -- to treat the deadly infection. The malaria pathogen targets a particular enzyme called PKC, which weakens the the protein chain, dismantling the cells and causing them to collapse. But sotrastaurin blocks P. falciparum's interaction with PKC.
Without that interaction, Greenbaum says, the parasites can’t reproduce.
“They are sort of trapped inside the host cell and if they can’t get out, they can’t continue their lifecycle and within a couple of hours, they start to die,” Greenbaum said.
Researchers led by Greenbaum tested the experimental drug, now in clinical trials to prevent organ rejection in transplant patients, and the compound dramatically reduced the number of P. falciparum malaria parasites in infected laboratory mice.
Because sotrastaurin targets human cellular proteins, Greenbaum says P. falciparum can’t develop resistance to the drug which has made quinine and artemisinin drugs to treat malaria less effective in recent years.
An article by Doron Greenbaum and colleagues at John Hopkins University in Baltimore, Maryland describing how the malaria parasite reproduces itself is published in the journal Cell, Host and Microbe.